The elimination of T. infestans from the remaining infested Chagas-disease endemic areas of the Southern Cone presents difficult challenges because of limited resources, atypical ecology, and biological and operational obstacles to vector control. Southern Peru is a prime example: delays in implementing control measures, massive rural to urban migration, and densely situated houses built on and of volcanic rock have resulted in complex urban transmission cycles. Innovative strategies are needed to ensure the success of vector control in Peru; failure to do so puts neighboring countries at risk for re-infestation by the vector and jeopardizes the entire Southern Cone Initiative. Recent introduction of vectors and parasite into the city of Arequipa itself allows analysis of the trend of urbanization of Chagas disease transmission and identification of modifications necessary to eliminate the vector from the urban environment. We plan to use modern molecular tools and spatial analysis to identify similarities that link rural and urban foci to understand how the ecology and epidemiology of the urban and periurban environment differs from that in traditional rural endemic zones. The overall aim of Research Project 1 is to develop strategies for control of Chagas disease based on a comparative analysis of transmission patterns in rural and urban communities, using ecologic, epidemiologic, qualitative and spatial methods in concert with high resolution molecular characterization of Trypanosoma cruzi and Triatoma infestans. The methods will include a rigorous analysis of the ecology and epidemiology of human Chagas disease and its vector in contrasting rural and peri-urban sites with ongoing vectorial T.cruzi transmission, using assessment of human, animal, and vector T.cruzi infections rates and spatial patterns, and a qualitative study of human migration and animal husbandry patterns. Studies of vector reinfestion utilizing population genetics analyses of recently developed T. infestans microsatellite markers and dynamic risk maps of reinfestation risk will provide improved guidance for residual insecticide application and post application surveillance for re-infestation, especially in peri-urban settings. Finally we will use georeferenced data on infestation and T. cruzi infected vectors to improve the efficiency of targeted serologic screening to identify T.cruzi infected children. The data from this Project will have immediate applicability for the regional Chagas disease control program in Arequipa and in other endemic areas.